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      Do patients with Prader–Willi syndrome have favorable glucose metabolism?

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          Abstract

          Background

          In recent years, more studies have observed that patients with Prader–Willi syndrome have lower insulin levels and lower insulin resistance than body mass index-matched controls, which may suggest protected glucose metabolism.

          Method

          The PubMed and Web of Science online databases were searched to identify relevant studies published in the English language using the terms “Prader–Willi syndrome” with “glucose”, “insulin”, “diabetes mellitus”, “fat”, “adipo*”, “ghrelin”, “oxytocin”, “irisin” or “autonomic nervous system”.

          Results

          The prevalence of impaired glucose intolerance, type 2 diabetes mellitus and some other obesity-associated complications in patients with Prader–Willi syndrome tends to be lower when compared to that in general obesity, which is consistent with the hypothetically protected glucose metabolism. Factors including adipose tissue, adiponectin, ghrelin, oxytocin, irisin, growth hormone and the autonomic nervous system possibly modulate insulin sensitivity in patients with Prader–Willi syndrome.

          Conclusion

          Although lower insulin levels, lower IR and protected glucose metabolism are widely reported in PWS patients, the causes are still mysterious. Based on existing knowledge, we cannot determine which factor is of utmost importance and what are the underlying mechanisms, and further research is in urgent need.

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          Most cited references154

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          A PGC1α-dependent myokine that drives browning of white fat and thermogenesis

          Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be a protein therapeutic for human metabolic disease and other disorders that are improved with exercise.
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            The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

            Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.
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              Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

              Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.
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                Author and article information

                Contributors
                zcc14@zju.edu.cn
                Journal
                Orphanet J Rare Dis
                Orphanet J Rare Dis
                Orphanet Journal of Rare Diseases
                BioMed Central (London )
                1750-1172
                7 May 2022
                7 May 2022
                2022
                : 17
                : 187
                Affiliations
                [1 ]GRID grid.411360.1, Department of Endocrinology, The Children’s Hospital of Zhejiang University School of Medicine, , National Clinical Research Center for Child Health, ; No 3333 Binsheng Road, Hangzhou, 310051 China
                [2 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Genetics, , Yale University School of Medicine, ; New Haven, USA
                Author information
                http://orcid.org/0000-0002-4667-3636
                Article
                2344
                10.1186/s13023-022-02344-3
                9077846
                35525976
                8ac5ce3b-b5d3-4a14-a903-7a60f100663d
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 8 January 2022
                : 26 April 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81371215
                Award ID: 81670786
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100019166, Department of Transportation of Zhejiang Province;
                Award ID: 2021 C03094
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Infectious disease & Microbiology
                prader–willi syndrome,insulin,insulin resistance,adipose,hormones

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